International Publication Number WO 89/10369 discloses compounds of the formula: ##STR2## wherein:
one of a, b, c and d represents nitrogen or --NR.sup.11 --, wherein R.sup.11 is O.sup.--, --CH.sub.3 or --(CH.sub.2).sub.p CO.sub.2 H wherein p is 1 to 3, and the remaining a, b, c and d groups are CH which may be substituted with R.sup.1 or R.sup.2 ;
R.sup.1 or R.sup.2 may be the same or different and each independently represents halo, --CF.sub.3, --OR.sup.10, --C(O)R.sup.10, --S(O).sub.e R.sup.12 wherein e is 0, 1, or 2, --N(R.sup.10).sub.2, --NO.sub.2, SH, CN, --OC(O)R.sup.10, --CO.sub.2 R.sup.10, --OCO.sub.2 R.sup.12, --NR.sup.10 C(O)R.sup.10, alkyl, alkenyl or alkynyl, which alkyl or alkenyl groups may be substituted with halo, --OR.sup.10 or --CO.sub.2 R.sup.10, or R.sup.1 and R.sup.2 may together form a benzene ring fused to the pyridine ring;
R.sup.10 represents H, alkyl or aryl;
R.sup.12 represents alkyl or aryl;
R.sup.3 and R.sup.4 may be the same or different and each independently represents H or any of the substituents of R.sup.1 and R.sup.2, or R.sup.3 and R.sup.4 may be taken together to represent a saturated or unsaturated C.sub.5 to C.sub.7 ring fused to the benzene ring;
R.sup.5, R.sup.6, R.sup.7, and R.sup.8 each independently represents H, --CF.sub.3, --CO.sub.2 R.sup.10, --C(O)R.sup.10, alkyl or aryl, which alkyl or aryl may be substituted with --OR.sup.10, --SR.sup.10, --N(R.sup.10).sub.2, --NO.sub.2, --C(O)R.sup.10, --OC(O)R.sup.12, --CO.sub.2 R.sup.10 and --OPO.sub.3 (R.sup.10).sub.2, or one of R.sup.5, R.sup.6, R.sup.7, and R.sup.8 may be taken in combination with R as defined below to represent --(CH.sub.2).sub.r wherein r is 1 to 4, said combination being optionally substituted with lower alkyl, lower alkoxy, --CF.sub.3 or aryl, or R.sup.5 may be combined with R.sup.6 to represent .dbd.O or .dbd.S, and/or R.sup.7 may be combined with R.sup.8 to represent .dbd.O or .dbd.S;
T represents carbon or nitrogen, with the dotted line attached to T representing an optional double bond when T is carbon;
m and n are integers 0, 1, 2, or 3, such that the sum of m plus n equals 0 to 3;
when m plus n equals 1, X represents --O--, --S(O).sub.e -- wherein e is 0, 1 or 2, --NR.sup.10 --, --C(O)NR.sub.10 --, --NR.sup.10 C(O)--, C(S)NR.sup.10 --, --NR.sup.10 C(S)--, --C(O).sub.2 -- or --O.sub.2 C--, wherein R.sup.10 is as defined above;
when m plus n equals 2, X represents --O--, --S(O).sub.e wherein e is 0, 1 or 2, or --NR.sup.10 --;
when m plus n represents 0, X can be any substituent for m plus n equalling 1 and X can also be a direct boned, cyclopropylene or propenylene;
when m plus n equals 3 then X equals a direct bond;
each R.sup.a may be the same or different, and each independently represents H, lower alkyl or phenyl;
Z represents .dbd.O, .dbd.S or .dbd.NR.sup.13 with R.sup.13 equal to R.sup.10 or --CN, wherein R.sup.10 is as defined above, such that
(a) when Z is O, R may be taken in combination with R.sup.5, R.sup.6, R.sup.7 or R.sup.8 as defined above, or R represents H, alkyl, aryl, --SR.sup.12, --N(R.sup.10).sub.2, cycloalkyl, alkenyl, alkynyl or --D wherein --D represents heterocycloalkyl, ##STR3## wherein R.sup.3 and R.sup.4 are as previously defined, and W is O, S or NR.sup.10, and wherein Y is N or NR.sup.11,
said cycloalky, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R.sup.10).sub.2, aryl, --CO.sub.2 R.sup.10, --OR.sup.14, --SR.sup.14, --N(R.sup.10).sub.2, --N(R.sup.10)CO.sub.2 R.sup.10, --COR.sup.14, --NO.sub.2 or --D, wherein --D and R.sup.10 are as defined above and R.sup.14 represents R.sup.10, --(CH.sub.2).sub.r OR.sup.10 or --(CH.sub.2).sub.q CO.sub.2 R.sup.10 wherein r is 1 to 4, q is 0 to 4; said alkeny and alkynyl R groups not containing --OH, --SH, or --N(R.sup.10).sub.2 on a carbon in a double or triple bond respectively; and
(b) when Z represents .dbd.S, R represents in addition to those R groups above, aryloxy or alkoxy; and
(c) where Z represents .dbd.NR.sup.13, R represents H, alkyl, aryl, N(R.sup.10).sub.2, cycloalkyl, alkenyl or alkynyl.
WO 89/10369 generically discloses compounds which can have the structure: ##STR4## wherein Z can be O and R can be: ##STR5## wherein Y can be NR.sup.11 and R.sup.11 can be --O.sup.-- ; however, no specific compounds are disclosed with this structure.
U.S. Pat. No. 4,826,853 issued to Piwinski et al. on May 2, 1989 is the priority document for WO 88/03138 which publisehd on May 5, 1988. WO 88/03138 discloses compounds of the formula: ##STR6## The various substituent groups are described on pages 2 to 3 of WO 88/03138. For example, X represents N or C, which C may contain an optional double bond to carbon atom 11; the dotted line between carbon atoms 5 and 6 represents an optional double bond and when no double bond is present A and B can be, amongst other groups, H.sub.2 ; Z can be amongst other atoms, O and R can be, amongst other substituents, alkyl or ##STR7##
WO 90/13548 published on Nov. 15, 1990 on PCT/US90/02251 which was filed on Apr. 30, 1990 and claims priority to U.S. application Ser. No. 345,604 filed May 1, 1989 discloses compounds similar in structure to the compounds disclosed in WO 88/03138 with the difference being that the R group represents and N-oxide heterocyclic group of the formula (i), (ii), (iii), or (iv): ##STR8## wherein R.sup.9, R.sup.10, and R.sup.11 can be, amongst other groups, H.
Copending U.S. application Ser. No. 625,261 filed on Dec. 10, 1990 is related to WO 90/13548.
The following references have disclosed oxygen or sulfur in the bridgehead of the three ring portion of the molecule:
(1) Canadian Application 780,443, published in the name of Sandoz Patents Ltd.;
(2) Eire 17764, published Apr. 5, 1964 in the name of Sandoz Patents Ltd.;
(3) European Patent Application 81816337.6, Sandoz A.G., published Mar. 10, 1982;
(4) Belgian Application 638,971, Sandoz S.A., published Apr. 21, 1964;
(5) Belgian Application 644,121, Sandoz S.A., published Aug. 20, 1964;
(6) U.S. Pat. No. 4,609,664, issued to Hasspacher on Sep. 2, 1986;
(7) U.S. Pat. No. 3,966,944, issued to Carter on Jun. 29, 1976;
(8) U.S. Pat. No. 3,803,153, issued to Villani on Apr. 9, 1974;
(9) U.S. Pat. No. 3,803,154, issued to Drukker on Apr. 9, 1974; and
(10) U.S. Pat. No. 3,325,501, issued to Ettinsen et al. on Jun. 13, 1967.
None of references (1) to (10) above disclose substitution on the piperidylidene nitrogen similar to that described below for the compounds of this invention.